The present invention relates to a rapidly polymerizing, ionic, conformable, electrically conductive adhesive for use in disposable biomedical electrodes, and to a method for production of such electrodes. More particularly, this invention relates to an electrically conductive, adhesive hydrogel that does not require the addition of a humectant or plasticizer, and that can polymerize in less than 30 seconds to produce an essentially dry conductive adhesive that is easily removed. The adhesive may also be used as a nonconductive biomedical adhesive in, for example, occlusive bandages, ostomy gaskets, and drug delivery systems.
The need for conductive adhesives useful in biomedical electrodes is well-documented in the art. To have utility, the adhesive should have good electrical conductivity, conform well to the skin surface, and be sufficiently adhesive to maintain a stable connection with the skin surface, yet be cohesive enough to pull away readily from the skin without leaving a residue when the electrode is removed. In addition, the electrode should be easy to manufacture, and easy to package.
Conductive adhesives used in currently available biomedical electrodes are generally "dry" gel adhesives composed primarily of a crosslinked synthetic polymer or interpolymer matrix. The gel is formed by dispersing a polymer or polymer mix in a solvent, applying the viscous liquid to the surface where adhesive properties are desired, and then crosslinking the polymers by exposing them to ionizing radiation, (X-ray, gamma, or electron beam radiation), or to heat. Alternatively, a crosslinking agent may be added to the solution and crosslinking may be induced by means of a chemical catalyst or by a photoinitiator and UV light. The act of crosslinking will absorb a certain amount of liquid, and as long as the initial liquid content is not too great, the crosslinked product formed is a "dry"gel or film. In some cases, especially if the solvent is aqueous, it may be necessary to let the crosslinked matrix stand overnight in air, or under nitrogen, to evaporate unbound water.
Appropriate combinations of interpolymers also have the effect of forming a solid matrix, although because they are not crosslinked they cannot absorb as much liquid. Gum karaya, a swellable, naturally-occuring ionic polymer base, has also been used as a matrix. However, the inability to control its chemical and physical properties, and the gum's potential for stimulating adverse skin reactions and microbial growth have limited its utility.
The gel adhesives of the art typically also comprise water and a polyhydric alcohol in addition to the polymer. Water provides excellent electrical conductivity properties. However, the optimum water content for electrical conductivity is often compromised in an effort to achieve better adhesion and cohesion. Polyhydric alcohols such as polyethylene glycol are generally added in substantial amounts (30-50%) as humectants or plasticizers to increase the conformability of the adhesive. A humectant is especially important when gels are formed substantially of homopolymers, as these gels tend to be brittle. Such concentrations of polyhydric alcohols can be irritating to the skin.
Ionizing salts are generally added to provide electrical conductivity, although in some cases water-soluble polymers or ionic polymers are relied on to provide conductivity. In this case, a neutralizing base may be added to promote the ionic properties of, for example, acrylic acid.
Other additives, particularly tackifiers, also may be added to the composition. However, tackifiers have not been found particularly helpful in optimizing the electrical adhesive properties of such compositions. In addition, prolonged storage tends to diminish the tack in these compositions, possibly as a result of esterification crosslinking of the tackifier.
The gel adhesives of the art contain a number of deficiencies, among them, the requirement for a polyhydric alcohol, a maximum aqueous volume that is lower than the optimum level for electrical conductivity, and an inefficient and costly synthesis process.
U.S. Pat. Nos. 4,699,146; 4,750,482; and 4,772,954 all claim compositions of polymers that are cross-linked in situ by exposure to high energy radiation (approximately 0.25-5.0 millirads). The '146 and '482 patents, (both to Sieverding), disclose a matrix of polyvinylpyrrolidone, polyethylene glycol and water. The '954 patent (Keusch et al.), discloses a polyethylene oxide-water matrix that may contain an ionizing salt.
In addition to being expensive and posing severe space constraints, high energy radiation can produce undesired reactive species. This makes use of the process difficult to control and makes the effect of additional constituents difficult to predict.
U.S. Pat. No. 4,593,053 (Jevne et al.) discloses a hydrogel comprising polyvinylpyrrolidone, water, a polyvinyl alcohol, a polyhydric alcohol humectant, and salt. The composition is first heated to 130.degree. C. to crosslink the polymer, then applied to the desired surface and allowed to cool in air to a non-liquid state.
EPO 168,917 discloses a polyacrylamide-disaccharide composition that includes a crosslinking agent and water, and which polymerizes in air in 30 minutes in the presence of a chemical catalyst.
U.S. Pat. Nos. 4,352,359 and 4,273,135 (both to Larimore et al.) disclose compositions of interpolymers and plasticizers. The adhesives may also include tackifiers. The interpolymers are not crosslinked, which limits the amount of solution or polar humectant the matrix can absorb. The compositions are knife-coated onto the electrode and allowed to air dry overnight.
U.S. Pat. No. 4,391,278 (Cahalan et al.) discloses a composition comprising 2-acrylamido-2-methopropanesulfonic acid, a humectant, water and a tackifier. Crosslinking occurs under nitrogen in five minutes in the presence of a chemical initiator.
The time and/or space constraint imposed by the cross-linking or "curing" step in each of the above patents limits their utility when the mass production of the compositions is considered. Compositions that require nitrogen chambers or high radiation sources for polymerization would require substantial increased expenses in equipment, production space and power. Adhesives that require substantial polymerization or drying time would require the allocation of too much valuable production space to render their mass production cost-efficient.
Recently, another method of gel adhesive formation has been developed. The method involves forming a precursor solution of monomers and other desired components, applying this viscous precursor to the electrode and allowing polymerization and crosslinking of the monomers to occur together. This method allows the absorption of a larger volume of the solvent. Typically the solvents are aqueous and the adhesives are referred to as hydrogels. The ability to absorb larger aqueous volumes allows one to take advantage of the superior conductive properties of water. However, the choice of monomers in the hydrogels has limited the amount of water the matrix can absorb without losing tack and cohesion. Moreover, the preferred hydrogels of the art still incorporate substantial amounts of humectants or plasticizers for conformability
U.S. Pat. Nos. 4,524,087, 4,554,924, 4,539,996 and 4,848,353 (all to Engel) disclose monomeric adhesive precursor compositions that are polymerized in situ in the presence of a crosslinking agent, a photoinitiator, and UV light.
The '087 and '996 Engel patents require at least one ionic monomer, a polyhydric alcohol, a crosslinker, water, a neutralizing base, and an initiator. The ionic monomers listed are salts of unsaturated carboxylic acids The '924 patent discloses a similar composition but comprising nonionic monomers instead of ionic monomers, and does not require a neutralizing base. An aqueous solution comprising an ionizing salt provides electrical conductivity. The nonionic monomer is acrylic acid or N-vinyl pyrrolidone, and in all examples discloses a tackifier to provide sufficient tack.
The '353 patent discloses a copolymer matrix of hydrogen bond donating monomers and hydrogen bond accepting monomers (a carboxylic acid and N-vinyl pyrrolidone, respectively) The monomers are present in a particular ratio (1:2 to 3:1, acid to pyrrolidone), and the hydrogen bond donating sites must be between about 5% to 80% neutralized (by addition of a neutralizing base such as sodium hydroxide, for example) Increasing the concentration of the vinyl pyrrolidone under these conditions yields soft hydrogels that leave a residue on the skin upon removal (EPO 322,098). Covalent cross-linking and humectants are purportedly not required, although a crosslinking agent is included in all examples described, and all preferred electrode adhesives contain about 50% glycerol
The Engel hydrogels (0.1-0.8 mm thick) all require one to four minutes of curing in a three-foot inert nitrogen atmosphere chamber under a bank of 30 18" "black light" UV tubes. The maximum "curing" production rate would thus be about 180 feet per hour. In addition, nitrogen chambers are expensive. Although the production rate could be increased by using a larger chamber, it would require an increased expense in equipment, allocation of production space for the larger chamber, and the added cost of powering the large bank of UV lamps and larger supply of nitrogen. Eliminating the nitrogen chamber would require longer curing times and/or a greater intensity of UV light, as UV radiation is less efficient in air.
U.S. Pat. No. 4,842,768 (Nakao, et al.) claims a hydrogel adhesive formed of an ionic monomer, two different alkyl methacrylates, a polyhydric alcohol, a photoinitiator, and water. The composition is polymerized under nitrogen by exposure to UV light from "two parallely disposed 30 W" chemical lamps for five minutes.
EPO 322,098 (Duan) discloses hydrogel adhesives comprised of one monomeric species (N-vinyl pyrrolidone), water, a polyhydric alcohol, a photoinitiator and a particular class of crosslinking agents (multiethylenically unsaturated compounds containing vinyl, allyl or methallyl groups bonded to nitrogen or oxygen atoms). The use of N-vinylpyrrolidone as the primary polymer precursor allows the composition to absorb polar liquids. However, a humectant is still required in these compositions. Curing is said to occur within 0.5 minutes to 5 hours "depending on the intensity of the radiation and the opacity of the adhesive " Optimum conditions for curing a 0.89 mm thick gel appear to require curing at a distance of approximately 1 foot and curing times on the order of 10 to 15 minutes. Decreasing the curing distance between the adhesive and the UV source to about 6 inches would reduce curing times to about five minutes.
None of the adhesives of the art succeed at providing all the requirements for a cohesive, conformable biomedical adhesive that can be efficiently produced and does not require substantial quantities of a humectant. Accordingly, it is an object of this invention to provide a hydrogel for use as a biomedical adhesive that has superior adhesive and cohesive properties and that can be produced efficiently. Other objects are to provide a hydrogel adhesive that does not require a humectant; to provide an adhesive with superior conductive properties without compromising the requirement for adhesion and cohesion; and to provide a hydrogel adhesive that is capable of being cured rapidly and efficiently, e.g, in substantially less than 30 seconds when exposed to light from a UV lamp providing 200 Watts per linear inch intensity.
Another object is to provide a method for producing a rapidly polymerizing adhesive.
These and other objects and features of the invention will be apparent from the description, drawing, and claims that follow.